Genome-wide association and functional interrogation identified a variant at 3p26.1 modulating ovarian cancer survival among Chinese women.

Abstract

Ovarian cancer survival varies considerably among patients, to which germline variation may also contribute in addition to mutational signatures. To identify genetic markers modulating ovarian cancer outcome, we performed a genome-wide association study in 2130 Chinese ovarian cancer patients and found a hitherto unrecognized locus at 3p26.1 to be associated with the overall survival (Pcombined = 8.90 × 10-10). Subsequent statistical fine-mapping, functional annotation, and eQTL mapping prioritized a likely casual SNP rs9311399 in the non-coding regulatory region. Mechanistically, rs9311399 altered its enhancer activity through an allele-specific transcription factor binding and a long-range interaction with the promoter of a lncRNA BHLHE40-AS1. Deletion of the rs9311399-associated enhancer resulted in expression changes in several oncogenic signaling pathway genes and a decrease in tumor growth. Thus, we have identified a novel genetic locus that is associated with ovarian cancer survival possibly through a long-range gene regulation of oncogenic pathways.

• Authors: Hongji Dai, Xinlei Chu, Qian Liang, Mengyun Wang, Lian Li, Yao Zhou, Zhanye Zheng, Wei Wang, Zhao Wang, Haixin Li, Jianhua Wang, Hong Zheng, Yanrui Zhao, Luyang Liu, Hongcheng Yao, Menghan Luo, Qiong Wang, Shan Kang, Yan Li, Ke Wang, Fengju Song, Ruoxin Zhang, Xiaohua Wu, Xi Cheng, Wei Zhang, Qingyi Wei, Mulin Jun Li, Kexin Chen
• Journal: Cell discovery (Cell Discov) Vol. 7 Issue 1 Pg. 121 (Dec 21 2021) ISSN: 2056-5968 [Print] England
• PMID: 34930913 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).